Genomic patterns of pleiotropy and the evolution of complexity

Abstract

Pleiotropy refers to the phenomenon of a single mutation or gene affecting multiple distinct phenotypic traits and has broad implications in many areas of biology. Due to its central importance, pleiotropy has also been extensively modeled, albeit with virtually no empirical basis. Analyzing phenotypes of large numbers of yeast, nematode, and mouse mutants, we here describe the genomic patterns of pleiotropy. We show that the fraction of traits altered appreciably by the deletion of a gene is minute for most genes and the gene-trait relationship is highly modular. The standardized size of the phenotypic effect of a gene on a trait is approximately normally distributed with variable SDs for different genes, which gives rise to the surprising observation of a larger per-trait effect for genes affecting more traits. This scaling property counteracts the pleiotropy-associated reduction in adaptation rate (i.e., the "cost of complexity") in a nonlinear fashion, resulting in the highest adaptation rate for organisms of intermediate complexity rather than low complexity. Intriguingly, the observed scaling exponent falls in a narrow range that maximizes the optimal complexity. Together, the genome-wide observations of overall low pleiotropy, high modularity, and larger per-trait effects from genes of higher pleiotropy necessitate major revisions of theoretical models of pleiotropy and suggest that pleiotropy has not only allowed but also promoted the evolution of complexity.genetics | adaptation | modularity | yeast | phenotype

The ubiquity of pleiotropy in human disease

“…Nonetheless, based on the current results, we conclude that effect size correlates positively with pleiotropy. This conclusion is also supported by previous work from non-human studies (Pickrell et al 2016;Visscher and Yang 2016;Wang et al 2010). Three (non-mutually exclusive) hypotheses may explain why effect size scales positively with level of pleiotropy:…”

“…One study, using QTL associations addressed the relationship in sticklebacks between the degree of pleiotropy and allelic effect sizes, found a positive correlation (Albert et al 2008;Wagner and Zhang 2011). Similar results have also been found in a variety of model organisms (Wang et al 2010). While such studies are useful, no comparable study has ever been done to address this relationship with human disease.…”

Gene Functional Trade-Offs and the Evolution of Pleiotropy

“…Recent observations in a variety of species have found that the extent of pleiotropy varies among genes and is often limited, with a majority of genes influencing a small set of traits while a few genes affect many traits (Dudley et al 2005; Albert et al 2008;Wagner et al 2008;Wang et al 2010;Wagner and Zhang 2011). This is in direct opposition to the historical assumption of universal pleiotropy underlying most population and quantitative genetics approaches to the joint evolution of multiple characters (Fisher 1930;Lande 1979;Orr 1998).…”

“…This claim has been verified in theoretical studies based on Fisher's geometrical model (Chevin et al 2010;Lourenço et al 2011). Pleiotropy is consequently seen as a constraint on evolution because it reduces the adaptive capacity of an organism (Orr 2000;Welch and Waxman 2003).Recent observations in a variety of species have found that the extent of pleiotropy varies among genes and is often limited, with a majority of genes influencing a small set of traits while a few genes affect many traits (Dudley et al 2005; Albert et al 2008;Wagner et al 2008;Wang et al 2010;Wagner and Zhang 2011). This is in direct opposition to the historical assumption of universal pleiotropy underlying most population and quantitative genetics approaches to the joint evolution of multiple characters (Fisher 1930;Lande 1979;Orr 1998).…”

CHARACTERIZATION OF SOME INDIAN SESAME (Sesamum indicum L.) CULTIVARS THROUGH SOLUBLE SEED STORAGE PROTEIN MARKERS

“…An insight into characterization and preservation of naturally existing variation in sesame, therefore, has become a necessity for further improvement of the crop. Phenological traits, due to pleiotropic effect and polygenic control, exhibit overlapping variation within and between species populations offering taxonomic complexity (Huber-Morath & Phlomis, 1982;Wang et al, 2010;Pabby & Rockman, 2013). Soluble seeds storage protein markers assessed through Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (SDS-PAGE) had been successfully employed to characterize cultivated varieties in several crop plant species, of which Mung (Ghaffor et al, 2002), Pea (Jha & Ohri, 2002), Einkorn wheat (Alvarez et al, 2006), Brassica (Khurshid & Rabbani, 2012) are few to name.…”